The purpose of this project is to study the action of diphtheria toxin at the cellular and molecular level, and to compare and contrast the action of pseudomonas exotoxin A, as this toxin has the same cellular target but a different mechanism of entry into the cell. Our major objectives include: 1) Determinaion of the presence and activity of toxin-specific receptor sites and determination of the mechanism by which diphtheria toxin is activated and enters cells, 2) Determination of the cellular and molecular basis for the resistance to diphtheria toxin found in some cells and animal species, 3) Elucidation of steps which lead to inhibition of protein synthesis in intoxicated cells, 4) Extension of our study to include the interaction of toxin-sensitive and toxin-resistant cells with biologically active agents which either compete with or enhance the action of diphtheria toxin.